Events

Videos

Podcasts

Articles

Society for Neuro-Oncology Annual Meeting

The combination of bevacizumab and lomustine showed superior efficacy compared with either agent alone in patients with recurrent glioblastoma, warranting further study, according to the phase II BELOB study presented by Martin van den Bent, MD, at the 2014 Society for Neuro-Oncology’s (SNO) Annual Meeting in Miami.

It is crucial to research recurrent glioblastoma treatments because of a scarcity of available choices, “There are only a few modestly active chemotherapy options in recurrent glioblastoma,” van den Bent, from the Erasmus MC Cancer Institute in Rotterdam, Netherlands, said. Although bevacizumab is approved as a second-line treatment for glioblastoma, this approval was based on an open-label study. At this point, there are few well-controlled randomized studies to support its use for recurrent glioblastoma, van den Bent noted.

In the phase II multicenter BELOB trial, 148 patients were assigned to bevacizumab at 10 mg/kg on days 1, 15, and 29, bevacizumab at 10 mg/kg on day 1, 15, and 29 in combination with lomustine orally on day 1 (90 mg/m

Earlier in the trial, a preplanned safety review led to the reduction of the lomustine dose in the combination arm to 90 mg/m

, van den Bent said. The dose was lowered because of hematological-related adverse events. Subsequently, 8 patients were treated with bevacizumab plus lomustine at 110 mg/m

 and 44 patients were treated at the 90-mg/m

Patients in the study were enrolled between December 2009 and November 2011 and had histologically proven glioblastoma, a first recurrence after chemoradiation with temozolomide, and had finished radiotherapy more than 3 months before entering the study. Patients had adequate bone marrow, renal, and hepatic function. The median age was 57 years and the median World Health Organization performance status was 1. The trial’s primary endpoint was 9-month overall survival (OS).

At the analysis, 130 patients were reviewed for a response. The 9-month OS was 43% in the lomustine arm, 38% in the bevacizumab arm, and 59% in patients who received both agents. The investigator-assessed objective response rate was 5% in the lomustine arm, 38% in the bevacizumab arm, and 34% in the bevacizumab/lomustine arm.

The results do not support a continuation of treatment with bevacizumab alone. “There was a high response rate to single-agent bevacizumab, but it didn’t translate into overall survival,” van den Bent said.

Hypertension was the most frequently reported toxicity (26% of bevacizumab patients, 7% of lomustine patients, and 25% of bevacizumab and lomustine patients). Other commonly reported toxicities included fatigue (4%, 9%, and 18%, respectively) and infections (6%, 4%, and 11%, respectively). When BELOB trial results were reported in 

 earlier this year, 97% of patients had died, and 2% remained on treatment.

In secondary analyses, researchers found isocitrate dehydrogenase 1 (

) mutations in 8 patients. Progression-free survival and OS were longer in patients with IDH1 mutations compared with wild-type mutations. The 9-month OS was 60% for patients with the 

 mutation in the combination arm. Additionally, the 

 promoter was methylated in 47% of patients and also indicated better responses. Researchers suggest that patients with 

 mutations should be assessed in separate clinical trials and should even be excluded from trials in the recurrent setting, due to the inherently better outcomes seen.

Findings from the phase II BELOB trial met prespecified criteria for the establishment of a phase III trial. The combination of bevacizumab and lomustine are being studied in the randomized, controlled phase III study EORTC trial 26101 trial, with results expected by next year’s SNO meeting, van den Bent said.

	Taal W, OOsterkamp H, Walenkamp A, et al. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. 

View more from the 2014 Society for Neuro-Oncology Annual Meeting

The combination of bevacizumab and lomustine showed superior efficacy compared with either agent alone in patients with recurrent glioblastoma, warranting further study.

Adding Lomustine to Bevacizumab Improves Outcomes in Recurrent Glioblastoma

Roeland GW Verhaak, PhD, Assistant Professor, Department of Bioinformatics and Computational Biology, Division of Quantitative Sciences, The University of Texas MD Anderson Cancer Center, discusses a study that examined the comprehensive and integrative genomic characterization of diffuse lower grade gliomas.

Verhaak says this project took nearly 300 tumor samples from patients with lower grade glimoa and performed extensive molecular characterization on these samples. Researchers analyzed the data, searching for subtypes.

An unsupervised analysis showed the same pattern in every data set analyzed, Verhaak says, leading researchers to classify samples into 3 groups: astrocytoma, oligodendroglioma, and oligo-astrocytoma.

Verhaak says these 3 groups are important because they share disease biology, which could help researchers in clinical trials. The study also found that one of the groups is wild type for IDH, which is very similar to patients with giloblastomas. Because of this, these lower grade gliomas should be treated like glioblastomas, Verhaak says.

Dr. Verhaak Discusses Genomic Characterization of Diffuse Lower Grade Gliomas

In a phase III study, a combination of radiation therapy and procarbazine, CCNU, and vincristine (PCV) prolonged both overall survival (OS) and progression-free survival (PFS) compared with radiation therapy (RT) alone for patients with grade 2 glioma, said Jan C. Buckner, MD, chair of oncology, Mayo Clinic, Rochester, Minnesota.

 The benefit appeared strongest for patients with oligodendroglioma (O) and oligo-astrocytoma (OA).

Buckner reported the results during the initial Plenary Session at the 2014 Society for Neuro-Oncology’s (SNO) Annual Meeting in Miami. The study results build on Buckner and colleagues’ previous work presented earlier this year at the 2014 ASCO Annual Meeting. The report at ASCO focused on the long-term results of PCV given with RT,

 and found that grade 2 glioma patients with less than gross total tumor resection or who were aged ≥40 years experienced a prolonged OS and PFS compared with RT alone. In that report, males and patients with A or A-dominant OA had worse outcomes.

A 2012 report from the same group found an improvement in OS but not PFS in the patient group receiving RT and PCV versus RT alone.

The data reported at SNO focused on the treatment impact of RT alone versus RT and PCV combination therapy according to histologic type. The 251 patients included in the study were either aged <40 years with a subtotal resection or biopsy or aged >40 years with some type of resection and supratentorial grade 2 O, OA, or astrocytoma (A). Patients were accrued for the study between 1998 and 2002; 107 had O, 79 had OA, and 65 had A.

Patients were divided by age, histology, Karnofsky Performance Status, and the presence or absence of contrast enhancement on the preoperative imaging study. Patients were then randomized to RT alone (54 Gy in 30 fractions) or RT followed by 6 cycles of PCV chemotherapy. A log rank test was used to compare survival and PFS distributions for each histologic type.

Median OS for the PCV versus control arms was 13.3 versus 7.8 years (

 = .002) overall, and not reached versus 10.8 years (

 = .31), in the O, OA, and A cohorts, respectively. Median PFS was 10.4 versus 4 years overall (

 <.001), and not reached versus 6 years (

This is the first prospective study to show treatment-related survival as it relates to PCV and RT, Buckner said.

There were no treatment-related deaths. The most common side effects in the study were fatigue, anorexia, nausea, and vomiting. Nausea was more common with the RT and PCV combination. “The toxicity level was acceptable and similar to many chemotherapy options,” Buckner said.

Researchers next plan to assess RT versus the RT and PCV combination according to the molecular markers 1p/19q codeletion, 

 mutations, and genomic analyses. The hypothesis is that patients with 1p/19q deletion and 

 mutations will likely benefit from PCV, Bucker said.

Buckner et al’s study involved a collaboration of researchers from around the United States and Canada, including Wake Forest University, The University of Texas MD Anderson Cancer Center, Wayne State University School of Medicine, and Barrow Neurological Institute.

			Buckner J, Shaw E, Pugh S, et al. R9802: Phase III study of radiation therapy (RT) with or without procarbazine, CCNU, and vincristine (PCV) in low-grade qlioma: results by histologic type. Presented at: 19th Annual Meeting of the Society for Neuro-Oncology; November 13-16, 2014; Miami, FL. Abstract AT-13.

			Shaw EG, Wang M, Coons SW, et al. Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. 

The combination of radiation therapy with procarbazine, CCNU, and vincristine prolonged OS and PFS compared with radiation therapy alone in grade 2 glioma.

PCV Chemotherapy Plus Radiation Improves Survival in Low-Grade Glioma

Steven A. Toms, MD, director, neurosurgery, Geisinger Health System, discusses how targeting MEK can be an effective treatment strategy for CNS metastases.

Toms says he and his colleagues have been taking primary metastases cell lines out of bone and brain and analyzing them for genetic and epigenetic changes. The study showed that the MEK pathway was altered in a number of brain metastases, Toms says. These pathways are commonly deregulated in a wide variety of cancers.

Toms says this discovery may help researchers select specific targeted therapies to work on for treatment for these metastases. However, researchers might find that the cancer may be able to bypass the one pathway that is being inhibited. In order to combat that, Toms says, targeted therapies may need to be used in combination when targeting the MEK pathway.

Steven A. Toms, MD, director, neurosurgery, Geisinger Health System, discusses how targeting MEK can be an effective treatment strategy for CNS metastasis.

Society for Neuro-Oncology Annual Meeting | Conference

Adding Lomustine to Bevacizumab Improves Outcomes in Recurrent Glioblastoma

Dr. Verhaak Discusses Genomic Characterization of Diffuse Lower Grade Gliomas

PCV Chemotherapy Plus Radiation Improves Survival in Low-Grade Glioma

Dr. Toms on Targeting MEK as a Treatment Strategy for CNS Metastasis